This research will investigate the factors affecting the supply and recovery of cholesterol and cholesteryl esters from the plasma and the peripheral cells. Research in this laboratory has isolated and characterized for the first time a cholesteryl ester transfer protein from human plasma, and the program proposed will determine the interaction of this factor with lecithin:cholesterol acyltransferase and with specific cell receptors, in determining the balance between cholesterol uptake, cholesterol synthesis and cholesterol output in cultured fibroblasts, endothelial cells and vascular smooth muscle cells. Additionally we will examine the activity of subfractions of high-density lipoprotein, including those containing single apolipoproteins, on cellular cholesterol removal. Taken together, these experiments will provide information on the factors determining the proportions of high density and low density lipoprotein cholesterol in human plasma.